One of the commonest problems confronting the practicing physician is the management of hyperpyrexia. Because the armamentarium of available emergency antifebrile therapy is limited and, moreover, has inherent disadvantages, the purpose of the proposed study is to assess the suitability of the use of an 80% helium-20% oxygen environment as a new therapeutic measure in hyperpyretic crises. The potential antipyretic value of exposure to such a mixture is predicated upon the high thermal conductivity of helium, as compared to nitrogen, in O2, its proven clinical safety under many other conditions, and its case of administration. Its applicability as an antipyretic treatment mode will be evaluated by determining its cooling effectiveness during endotoxin-induced hyperprexia under various ambient thermal condition in adult and newborn guinea pigs. In this context also, the optimal conditions for the safe use of helium-oxygen as an antipyretic agent will be defined. Subsequently, based on the animal studies, its practicality and efficacy in reducing safely the body temperature of spontaneously febrile patients will be determined. If proven effective, the employment of such a helium-oxygen mixture in febrile crisis situations would provide a useful and readily available tool to obviate the deleterious sequelae of uncontrolled fever of any etiology.